TITLE: Boston Keratoprosthesis for the Treatment of Corneal Blindness: Clinical Effectiveness and Cost-Effectiveness DATE: 22 April 2016 CONTEXT AND POLICY ISSUES Corneal disease is the third most common cause of recoverable blindness in Canada, and the most common cause of visual handicap in Canadians under 30 years of age. 1-3 In 2013, 2,000 to 3,000 Canadians were on wait lists for corneal transplants. 4 In some instances, wait times were as long as three years. 5,6 Penetrating keratoplasty (PK), a corneal transplantation procedure to treat corneal blindness, is subject to complications such as infection, development of glaucoma, loss of visual acuity, and graft failure despite delivering positive visual outcomes. 7 Keratoprosthesis, an artificial cornea, was developed to treat patients whose corneas are at high risk for immunological rejection after PK, or corneas with factors that might predispose them to graft failure after a failed PK. 7,8 Implantation is performed by corneal surgeons, and visual acuity is assessed at baseline and at various time points postoperatively. Following the operation, every eye is treated with a bandage soft contact lens, which is changed on a monthly basis. Daily antibiotics are initiated and continued indefinitely. Boston keratoprosthesis, a new design of artificial cornea available in type 1 and type 2 configurations (with type 1 being the most common, and type 2 reserved for end-stage ocular surface disease desiccation), has resulted in positive clinical outcomes in the treatment of corneal blindness. It is also subject to complications, such as the development of retrosprosthetic membrane, glaucoma and infectious endophthalmitis. 9-14 This Rapid Response report aims to review the clinical and cost-effectiveness of Boston Type 1 (KPro) keratoprosthesis for the treatment of corneal blindness. Disclaimer: The Rapid Response Service is an information service for those involved in planning and providing health care in Canada. Rapid responses are based on a limited literature search and are not comprehensive, systematic review s. The intent is to provide a list of sources of the best evidence on the topic that CADTH could identify using all reasonable efforts w ithin the time allow ed. Rapid responses should be considered along w ith other types of information and health care considerations. The information included in this response is not intended to replace professional medical advice, nor should it be construed as a recommendation for or against the use of a particular health technology. Readers are also cautioned that a lack of good quality evidence does not necessarily mean a lack of effectiveness particularly in the case of new and emerging health technologies, for w hich little information can be found, but w hich may in future prove to be effective. While CADTH has taken care in the preparation of the report to ensure that its contents are accurate, complete and up to date, CADTH does not make any guarantee to that ef fect. CADTH is not liable for any loss or damages resulting from use of the information in the report. Copyright: This report contains CADTH copyright material and may contain material in w hich a third party ow ns copyright. This report may be used for the purposes of research or private study only. It may not be copied, posted on a w eb site, redistributed by email or stored on an electronic system w ithout the prior w ritten permission of CADTH or applicable copyright ow ner. Links: This report may contain links to other information available on the w ebsites of third parties on the Internet. CADTH does not have control over the content of such sites. Use of third party sites is governed by the owners own terms and conditions.
RESEARCH QUESTIONS 1. What is the clinical effectiveness of the Boston type 1 Keratoprosthesis for the treatment of corneal blindness? 2. What is the cost-effectiveness of the Boston type 1 Keratoprosthesis for the treatment of corneal blindness? KEY FINDINGS The evidence suggests that Boston keratoprosthesis (KPro) implantation has favourable visual acuity and graft retention, and lower complication rates. There was significant improvement in vision-related quality of life. In patients with advanced ocular surface conditions, (KPro) implantation, despite offering the potential for an efficient rehabilitation tool, can lead to postoperative infections that may compromise device retention and reduce visual outcomes. No evidence on the cost-effectiveness of the KPro for the treatment of corneal blindness was found. METHODS Literature Search Strategy A limited literature search was conducted on key resources including PubMed, The Cochrane Library, University of York Centre for Reviews and Dissemination (CRD) databases, Canadian and major international health technology agencies, as well as a focused Internet search. No filters were applied to limit the retrieval by study type. Where possible, retrieval was limited to the human population. The search was also limited to English language documents published between January 1, 2011 and March 23, 2016. Selection Criteria and Methods Table 1: Selection Criteria One reviewer screened the titles and abstracts of the retrieved publications and examined the full-text publications for the final article selection. Selection criteria are outlined in Table 1. Population Intervention Comparator Outcomes Study Designs Table 1: Selection Criteria Patients with a history of corneal graft failure (e.g., standard penetrating keratoplasty [PK]) Boston Type 1 Keratoprostheses (KPro) Penetrating PK corneal transplantation, no comparator Q1: Clinical effectiveness, safety (e.g. adverse events and complications including glaucoma, infection, graft failure, loss of vision) Q2: Cost-effectiveness Health technology assessments (HTAs), systematic reviews (SRs), meta-analyses (MAs), randomized controlled trials (RCTs), nonrandomized studies (NRS), and economic evaluations. Boston Keratoprosthesis for the Treatment of Corneal Blindness 2
Exclusion Criteria Articles were excluded if they did not meet the selection criteria in Table 1, if they were published prior to January 2011, if they were duplicate publications of the same study, or if they were referenced in a selected systematic review. Critical Appraisal of Individual Studies The quality of the included systematic review and clinical trials was assessed using the AMSTAR 15 and Downs & Black 16 checklists, respectively. Numeric scores were not calculated. Instead, the strengths and limitations of the study are summarized and presented. SUMMARY OF EVIDENCE Quantity of Research Available The literature search yielded 371 citations. After screening of abstracts from the literature search and from other sources, nine potentially relevant studies were selected for full-text review. Seven studies were included in the review. 17-23 The PRISMA flowchart in Appendix 1 details the process of the study selection. Summary of Study Characteristics A detailed summary of the included SR and clinical studies is provided in Appendices 2 and 3, respectively. Study design, setting, length of follow-up, year of publication One SR review and MA 17 and six clinical studies, including three pre and post prospective cohort studies 19,21,22 and three retrospective chart reviews 18,20,23 were included. The SR 17 included 26 primary studies with various settings which were published between 1990 and 2014 and enrolled a total of 29,855 eyes. The clinical studies, published between 2013 to 2016, were conducted in tertiary care centres with sample sizes that ranged from 24 to 300 eyes, and had a follow-up period between six and 32 months. 18-23 Population The SR included studies of participants with corneal opacity who had at least one failed PK. 17 One study also included patients with failed PKs. 18 The remaining clinical studies reported patients with various eye conditions eligible to KPro implantation. 19-23 The clinical studies included patients with a mean age ranging from 53.5 to 65.3 years old with various gender ratios. Comorbidities were not reported in any of the clinical studies. 18-23 Interventions and comparators The intervention was KPro procedure. 17-23 In the SR, the comparator was PK. 17 The remaining studies reported pre and post implantation outcomes or retrospective chart reviews. Outcomes Boston Keratoprosthesis for the Treatment of Corneal Blindness 3
The SR 17 and five clinical studies reported visual acuity, graft retention and complication rates. 17-20,22,23 One study reported patient-reported vision-related quality of life, using the National Eye Institute Visual Function Questionnaire (NEI VFQ-25). 21 Summary of Critical Appraisal Details of the strengths and limitations of the included studies are summarized in Appendix 4. The included SR provided an a priori design, performed a comprehensive literature search, and had independent studies selection and data extraction procedure in place. 17 The review, however, compared meta-analysis results (PK) to a retrospective case series (KPro). It included NRS, such as prospective and retrospective cohort studies, and case series. The review did not provide a list of included or excluded studies or describe the study characteristics and quality assessment of included studies. There was diversity across the studies in the underlying diagnosis for the intervention cohort (KPro), and no assessment of publication bias was performed. The included pre and post and retrospective clinical studies their hypothesis, selection method from the source population, patient characteristics, interventions, outcomes measured, main study results, estimates of random variability, and probability values provided losses to follow-up. 18-23 As the studies were non-randomized, there were potential selection or recall biases and confounding issues that may have affected the internal validity of the results. It is also not sure if they had sufficient power to detect a clinically important effect. Summary of Findings Main findings of included studies are summarized in detail in Appendix 5. 1. What is the clinical effectiveness of the Boston type 1 Keratoprosthesis for the treatment of corneal blindness? The SR evaluated KPro in patients with corneal opacity who had failed PKs. 17 Pooled estimates from 26 studies on PK were compared to results from one retrospective review of case series on KPro. Visual acuity had improved with KPro compared to repeat PK. The same trend was found in graft retention with KPro performing better than repeat PK. Fewer patients developed glaucoma at three years with repeat PK than with KPro. After 47 months follow-up, the proportion of patients with repeat PK who developed infectious keratitis was 18%. After five years follow-up, the proportion of patients with KPro who developed infectious keratitis was 2.9%, and infectious endophthalmitis was 10.3%. The authors concluded that KPro had favorable outcomes compared to repeat PK. A retrospective chart review evaluated the outcomes of KPro in 24 eyes with failed PK. 18 At a mean 28.9 months follow-up, post-operative best corrected 20/200 visual acuity as measured by the patient s best corrected visual acuity improved in 70.9% of eyes, remained unchanged in 12.5% of eyes, and was worse in 16.7% of eyes. KPro graft retention was retained in 91.7% of eyes. At least one serious complication occurred in 33.3% of eyes. The authors concluded that KPro is associated with satisfactory visual improvement and excellent prognosis for prosthesis retention in eyes with previous failed PKs. Boston Keratoprosthesis for the Treatment of Corneal Blindness 4
A pre and post prospective study examined the visual acuity in 300 eyes with advanced ocular surface diseases. 19 Visual acuity improved for 84.7% of eyes after an average of 17 months post-operation, and this improvement was retained for an average of 47.8 months. The authors concluded that KPro was an effective device for rehabilitation in advanced ocular surface disease. A retrospective chart review evaluated the complication rates of KPro in 52 eyes with advanced ocular surface conditions. 20 After a mean 37.7 months follow-up, post-operative infections occurred in 25.0% of eyes. Approximately 10.7% of procedures led to infectious keratitis, and 9.3% led to infectious endophthalmitis. Treatment of the infected eyes required prosthesis removal in 53.8% of eyes, and reduced pre-infection visual acuity in 53.8% of eyes. The authors concluded that postoperative infections were a serious issue that compromised device retention and visual outcomes after KPro implantation. A pre and post prospective study determined the impact of KPro on patient-reported visionrelated quality of life in 24 patients with various eye conditions undergoing KPro implantation. 21 Using the NEI VFQ-25, there were significant improvements in general vision, near and distance activities, social functioning, mental health, role difficulties, dependency, color vision, and peripheral vision compared with baseline values after a mean 16-month follow-up. The authors concluded that KPro significantly improved patients quality of life. A pre and post prospective study evaluated visual acuity, graft retention rates, and complication rates following KPro implantation in 30 eyes with various advanced eye conditions in Brazil. 22 After a mean 32 months follow-up, post-operative visual acuity improved in 80% of eyes. KPro was retained in 93.3% of eyes. Three eyes developed glaucoma, two eyes had retinal detachment, and one eye developed infectious keratitis. The authors concluded that KPro implantation was a viable option after failed PK or for conditions with poor prognosis for PK in a developing country. A retrospective chart review determined the visual outcomes and complications of KPro in 41 eyes with various advanced eye conditions. 23 Visual acuity was improved after a mean 22 months follow-up, and was maintained or improved in 82.92% of eyes. In terms of complications, the formation of retroprosthetic membrane occurred in 53.65% of eyes. Moreover, 4.87% of eyes had infectious keratitis, and 12.19% had infectious endophthalmitis. The authors concluded that KPro was an effective alternative in patients with ocular pathology and imminent risk of rejection of a new PK. The results from pre and post clinical studies and retroprospective chart reviews showed that KPro implantation had favorable visual acuity outcomes, graft retention and complication rates, such as the formation of glaucoma, retroprosthetic membrane and infections in patients with failed PKs. The study findings also suggested a significant improvement in vision-related quality of life, such as near and distance activities, social functioning, and mental health. In patients with advanced ocular surface conditions, KPro implantation, despite offering the potential of an efficient rehabilitation tool, may lead to postoperative infections that may compromise device retention and reduce visual outcomes. Boston Keratoprosthesis for the Treatment of Corneal Blindness 5
2. What is the cost-effectiveness of the Boston type 1 Keratoprosthesis for the treatment of corneal blindness? There was no evidence found on the cost-effectiveness of the KPro for the treatment of corneal blindness. Limitations The quality of the included studies is limited by the nature of their pre and post and chart review designs. One Canadian study was included in the review, so the generalizability of the findings of the remaining studies to the Canadian setting should be interpreted with caution. There was no evidence found on the cost-effectiveness of the KPro for the treatment of corneal blindness. CONCLUSIONS AND IMPLICATIONS FOR DECISION OR POLICY MAKING Results from the studies in this review indicate that KPro implantation had favorable visual acuity outcomes, graft retention and complication rates such as the formation of glaucoma, retroprosthetic membrane and infections in patients with failed PKs. The study findings suggested a significant improvement in vision-related quality of life such as near and distance activities, social functioning, and mental health. In patients with advanced ocular surface conditions, KPro implantation, despite offering the potential of an efficient rehabilitation tool, can lead to postoperative infections that may compromise device retention and reduce visual outcomes. Evidence on the clinical effectiveness and safety of KPro must be interpreted with caution since the quality of the included studies is limited by the nature of their non-randomized study designs with potential biases and confounding factors affecting the internal validity of the results such as selection and recall biases. There was no evidence found on the cost-effectiveness of the KPro for the treatment of corneal blindness. PREPARED BY: Canadian Agency for Drugs and Technologies in Health Tel: 1-866-898-8439 www.cadth.ca Boston Keratoprosthesis for the Treatment of Corneal Blindness 6
REFERENCES 1. Mertz E. Alberta takes steps to reduce wait times for cornea transplants [Internet]. [Edmonton]: Global News; 2013 Oct 23. [cited 2016 Mar 29]. Available from: http://globalnews.ca/news/921645/alberta-takes-steps-to-reduce-wait-times-for-corneatransplants/ 2. Demand for ocular tissue in Canada [Internet]. [Ottawa]: Canadian Blood Services; 2010 Jan. [cited 2016 Mar 29]. Available from: http://www.organsandtissues.ca/s/wpcontent/uploads/2011/11/demand_ocular_final1.pdf 3. A province by province comparison of cornea transplant wait times [Internet]. Winnipeg: CBC News; 2013. [cited 2016 Mar 26]. Available from: http://www.cbc.ca/manitoba/features/cornea/ 4. Teen athlete's sight restored [Internet]. [Ottawa]: Canadian Blood Services; 2014. [cited 2016 Mar 29]. Available from: http://www.cos-sco.ca/wpcontent/uploads/2014/02/canadianbloodservicesmetroad2014.pdf 5. Kramer L. Corneal transplant wait list varies across Canada. CMAJ [Internet]. 2013 Aug 6 [cited 2016 Mar 29];185(11):E511-E512. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/pmc3735757 6. Moore H. Cornea transplant system in Canada broken, say experts [Internet]. Winnipeg: CBC News; 2013 Mar 19. [cited 2016 Mar 26]. Available from: http://www.cbc.ca/news/canada/manitoba/cornea-transplant-system-in-canada-brokensay-experts-1.1380468 7. Tan DT, Dart JK, Holland EJ, Kinoshita S. Corneal transplantation. Lancet. 2012 May 5;379(9827):1749-61. 8. Keratoprosthesis restores vision in patients blinded by corneal disease [Internet]. London (UK): News-Medical.Net; 2014 Jun 20. [cited 2016 Mar 29]. Available from: http://www.news-medical.net/news/20140620/keratoprosthesis-restores-vision-in-patientsblinded-by-corneal-disease.aspx 9. Magalhães FP, de Sousa LB, de Oliveira LA. Boston type I keratoprosthesis: review. Arq Bras Oftalmol [Internet]. 2012 May [cited 2016 Mar 29];75(3):218-22. Available from: http://www.scielo.br/pdf/abo/v75n3/16.pdf 10. Behlau I, Martin KV, Martin JN, Naumova EN, Cadorette JJ, Sforza JT, et al. Infectious endophthalmitis in Boston keratoprosthesis: incidence and prevention. Acta Ophthalmol [Internet]. 2014 Nov [cited 2016 Mar 29];92(7):e546-e555. Available from: http://onlinelibrary.wiley.com/doi/10.1111/aos.12309/epdf 11. Chew HF, Ayres BD, Hammersmith KM, Rapuano CJ, Laibson PR, Myers JS, et al. Boston keratoprosthesis outcomes and complications. Cornea. 2009 Oct;28(9):989-96. 12. Bradley JC, Hernandez EG, Schwab IR, Mannis MJ. Boston type 1 keratoprosthesis: the University of California Davis experience. Cornea. 2009 Apr;28(3):321-7. Boston Keratoprosthesis for the Treatment of Corneal Blindness 7
13. Aldave AJ, Kamal KM, Vo RC, Yu F. The Boston type I keratoprosthesis: improving outcomes and expanding indications. Ophthalmology. 2009 Apr;116(4):640-51. 14. Akpek EK, Harissi-Dagher M, Petrarca R, Butrus SI, Pineda R, Aquavella JV, et al. Outcomes of Boston keratoprosthesis in aniridia: a retrospective multicenter study. Am J Ophthalmol. 2007 Aug;144(2):227-31. 15. Shea BJ, Grimshaw JM, Wells GA, Boers M, Andersson N, Hamel C, et al. Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol [Internet]. 2007 [cited 2016 Mar 29];7:10. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/pmc1810543/pdf/1471-2288-7-10.pdf 16. Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health [Internet]. 1998 Jun [cited 2016 Mar 29];52(6):377-84. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/pmc1756728/pdf/v052p00377.pdf 17. Ahmad S, Mathews PM, Lindsley K, Alkharashi M, Hwang FS, Ng SM, et al. Boston type 1 keratoprosthesis versus repeat donor keratoplasty for corneal graft failure: a systematic review and meta-analysis. Ophthalmology. 2016 Jan;123(1):165-77. 18. Hager JL, Phillips DL, Goins KM, Kitzmann AS, Greiner MA, Cohen AW, et al. Boston type 1 keratoprosthesis for failed keratoplasty. Int Ophthalmol. 2016 Feb;36(1):73-8. 19. Rudnisky CJ, Belin MW, Guo R, Ciolino JB, Boston Type 1 Keratoprosthesis Study Group. Visual acuity outcomes of the Boston keratoprosthesis type 1: multicenter study results. Am J Ophthalmol. 2016 Feb;162:89-98. 20. Wagoner MD, Welder JD, Goins KM, Greiner MA. Microbial keratitis and endophthalmitis after the Boston type 1 keratoprosthesis. Cornea. 2016 Apr;35(4):486-93. 21. Cortina MS, Hallak JA. Vision-related quality-of-life assessment using NEI VFQ-25 in patients after Boston keratoprosthesis implantation. Cornea. 2015 Feb;34(2):160-4. 22. de Oliveira LA, Pedreira Magalhaes F, Hirai FE, de Sousa LB. Experience with Boston keratoprosthesis type 1 in the developing world. Can J Ophthalmol. 2014 Aug;49(4):351-7. 23. Muñoz-Gutierrez G, Alvarez de Toledo J, Barraquer RI, Vera L, Couto Valeria R, Nadal J, et al. Post-surgical visual outcome and complications in Boston type 1 keratoprosthesis. Arch Soc Esp Oftalmol [Internet]. 2013 Feb [cited 2016 Mar 29];88(2):56-63. Available from: http://apps.elsevier.es/watermark/ctl_servlet?_f=10&pident_articulo=90198663&pident_us uario=0&pcontactid=&pident_revista=496&ty=96&accion=l&origen=zonadelectura&web= www.elsevier.es&lan=en&fichero=496v88n02a90198663pdf001.pdf Boston Keratoprosthesis for the Treatment of Corneal Blindness 8
Appendix 1: Selection of Included Studies 371 citations identified from electronic literature search and screened 362 citations excluded 9 potentially relevant articles retrieved for scrutiny (full text, if available) 0 relevant reports retrieved from other sources (grey literature, hand search) 9 potentially relevant reports 2 reports excluded (irrelevant population, interventions or outcomes) 7 reports included in review Boston Keratoprosthesis for the Treatment of Corneal Blindness 9
Appendix 2: Characteristics of Included Systematic Reviews First Author, Year, Country Ahmad, 17 2016, US, Saudi Arabia Table A1: Characteristics of Included systematic review Literature Search Strategy Articles with data regarding repeat PK published between 1990 and 2014 were identified in PubMed, EMBASE, the Latin American and Caribbean Health Sciences Literature Database, and the Cochrane Central Register of Controlled Trials and were reviewed. Results were compared with a retrospective review of consecutive, nonrandomized, longitudinal case series of KPro implantations performed at 5 tertiary care centers in the United States (p 165) Inclusion Criteria Exclusion Criteria Studies included Main outcomes We planned to include nonrandomized control trials, prospective and retrospective cohort studies, and interventional case series that were published between 1990 and 2014 (p 166) KPro: Boston type 1 keratoprosthesis; PK: penetrating keratoplasty. Studies that reported on fewer than 20 patients or cases were excluded (p 166) 26 studies (21 case series and 5 cohort studies) for PK 1 retrospective review of case series for KPro Visual acuity at 2 years (likelihood of attaining 20/200 or better) Graft retention at 5 years Glaucoma rate at 3 years Infection rate at 5 years Boston Keratoprosthesis for the Treatment of Corneal Blindness 10
Appendix 3: Characteristics of Included Clinical Studies First Author, Year, Country Table A2: Characteristics of Included clinical studies Study Objectives, design, Interventions/ Patients setting, length of follow-up Comparators Main Study Outcomes Hager, 18 2016, US The purpose of this study was to evaluate the outcomes of the Boston type 1 keratoprosthesis (Kpro-1) in eyes with failed keratoplasty (p 73) KPro PK 24 eyes Visual acuity (BCVA) Graft retention (in situ maintenance of the initial prosthesis) Retrospective chart review Tertiary care centre Complications (i.e, infectious keratitis, wound dehiscence) Mean 28.9 months follow-up Rudnisky, 19 2016, Canada, US Wagoner, 20 2016, US Cortina, 21 2015, US de Oliveira, 22 2014, Brazil To report improvement of visual outcomes of KPro Pre and post prospective study Tertiary care centre Mean 17 months follow-up To determine the incidence, ocular surface disease associations, microbiological profile, and clinical course of postoperative infections after implantation of the Boston type 1 keratoprosthesis (KPro-1) (p 486) Retrospective chart review Tertiary care centre Mean 37.7 months follow-up The aim of this study was to determine the impact of Boston keratoprosthesis (KPro) implantation on patient-reported visual function using the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) (p 160 Pre and post prospective study Tertiary care centre Mean 16 months follow-up To report the experience of the Federal University of São Paulo, Brazil, in performing Boston keratoprosthesis type 1 KPro 300 eyes Visual acuity (20/200 acuity) KPro 52 eyes Post-operative infections (i.e., infectious keratitis, endophthamitis) KPro 24 patients Vision-related quality of life (using the National Eye Institute Visual Function Questionnaire 25) KPro 30 eyes Visual acuity (BCVA) Graft retention (in situ maintenance of the initial Boston Keratoprosthesis for the Treatment of Corneal Blindness 11
First Author, Year, Country Table A2: Characteristics of Included clinical studies Study Objectives, design, Interventions/ Patients setting, length of follow-up Comparators implantation in the developing world (p 351) Pre and post prospective study Tertiary care centre Main Study Outcomes prosthesis)complications (i.e., development of glaucoma, infectious keratitis) Muñoz- Gutierrez, 23 2013, Spain Mean 32 months follow-up To describe the visual outcome of patients who underwent Boston type 1 keratoprosthesis (KPro1) implantation, and describe serious sight-threatening postoperative complications (p 56) Retrospective chart review Tertiary care centre KPro 41 eyes Visual acuity (BVCA) Complications (i.e., infectious keratitis, retroprosthetic membrane) Mean 22.17 months follow-up BVCA: best corrected visual acuity, KPro, KPro-1 or PPro1: Boston type 1 keratoprosthesis; NEI VFQ-25: National Eye Institute Visual Function Questionnaire 25; PK: penetrating keratoplasty. Boston Keratoprosthesis for the Treatment of Corneal Blindness 12
Appendix 4: Summary of Critical Appraisal of Included Studies Table A3: Summary of Critical Appraisal of Included Studies First Author, Publication Year Strengths Limitations Critical appraisal of included systematic review (AMSTAR 15 ) Ahmad, 17 2016 a priori design provided independent studies selection and data extraction procedure in place comprehensive literature search performed conflict of interest stated Critical appraisal of included clinical studies (Blacks & Down 16 ) Hager, 18 2016 hypothesis method of selection from source population and representation main outcomes, interventions, patient characteristics, and main findings estimates of random variability and actual probability values provided losses to follow-up Rudnisky, 19 2016 hypothesis method of selection from source population and representation main outcomes, interventions, patient characteristics, and main findings clearly estimates of random variability and actual probability values provided losses to follow-up Wagoner, 20 2016 hypothesis method of selection from source population and representation main outcomes, interventions, patient characteristics, and main findings estimates of random variability and actual probability values provided losses to follow-up Cortina, 21 2015 hypothesis method of selection from source population and representation comparing meta-analysis results (penetrating keratoplasty) to a retrospective case series (KPro) the meta-analysis included studies that are randomized controlled trials, prospective and retrospective cohort studies, and case series list of included studies and studies characteristics not provided list of excluded studies not provided quality assessment of included studies not provided and not used in formulating conclusions diversity in the underlying diagnosis for the intervention cohort (KPro) no assessment of publication bias performed retrospective chart review with potential recall bias and confounding factors not sure if study had sufficient power to detect a clinically important effect pre and post prospective cohort study with potential selection bias and confounding factors not sure if study had sufficient power to detect a clinically important effect retrospective chart review with potential recall bias and confounding factors not sure if study had sufficient power to detect a clinically important effect pre and post prospective cohort study with potential selection bias and confounding factors not sure if study had sufficient power to Boston Keratoprosthesis for the Treatment of Corneal Blindness 13
First Author, Publication Year Table A3: Summary of Critical Appraisal of Included Studies Strengths Limitations main outcomes, interventions, patient characteristics, and main findings estimates of random variability and actual probability values provided losses to follow-up de Oliveira, 22 2014 hypothesis method of selection from source population and representation main outcomes, interventions, patient characteristics, and main findings estimates of random variability and actual probability values provided losses to follow-up Muñoz-Gutierrez, 23 2013 hypothesis method of selection from source population and representation main outcomes, interventions, patient characteristics, and main findings estimates of random variability and actual probability values provided losses to follow-up detect a clinically important effect pre and post prospective cohort study with potential selection bias and confounding factors unclear if study had sufficient power to detect a clinically important effect retrospective chart review with potential recall bias and confounding factors not sure if study had sufficient power to detect a clinically important effect Boston Keratoprosthesis for the Treatment of Corneal Blindness 14
Appendix 5: Main Study Findings and Authors Conclusions Table A4: Main Study Findings and Authors Conclusions First Author, Publication Year Main Study Findings Authors Conclusions Research question 1 (clinical effectiveness of the Boston Keratoprosthesis (KPro) for the treatment of corneal blindness) Ahmad, 17 2016 Visual acuity (likelihood of maintaining 20/200 visual acuity or better at 2 years) Repeat PK: 42% (95% CI, 30% - 56%) KPro: 80% (95% CI, 68% - 88%) Graft retention (probability of maintaining a clear graft at 5 years) Repeat PK: 47% (95% CI, 40% - 54%) KPro: 75% (95% CI, 64% - 84%) Complications Glaucoma (proportion of patients at 3 years) Repeat PK: 25% (95% CI, 10% - 44%) KPro: 30% (CI not reported) These results demonstrate favorable outcomes of KPro surgery for donor corneal graft failure with a greater likelihood of maintaining visual improvement without higher risk of postoperative glaucoma compared with repeat donor PK (p 165) Hager, 18 2016 Rudnisky, 19 2016 Wagoner, 20 2016 Infection Repeat PK: (proportion of patients at 47 months follow-up) Infectious keratitis: 18% (95% CI, 9% - 30%) KPro: (proportion of patients after 5 years follow-up) Infectious keratitis: 2.9% (CI not reported) Infectious endophthalmitis: 10.3% (CI not reported) Visual acuity (BCVA improvement; mean 28.9 months followup) Post-operative BCVA improved in 17 (70.9%) eyes, unchanged in 3 (12.5%) eyes, worse in 4 (16.7%) eyes Graft retention (mean 28.9 months follow-up) KPro was retained in 22 (91.7%) eyes Complications (mean 28.9 months follow-up) One or more serious complications occurred in 8 (33.3%) eyes (among 1 case of wound dehiscence, 1 case of fungal keratitis, 4 cases of endophthalmitis, and 5 retinal detachments) Visual acuity improved (P < 0.0001) for 254 (84.7%) eyes (after mean 17 months post-op). This improvement was retained for an average 47.8 months. The median time to achieve 20/200 visual acuity was 1 month Procedures were performed in 52 eyes (mean 37.7 months follow-up) 8 cases (10.7%) developed infectious keratitis (fungal in 5 cases, bacterial in 3 cases) 7 cases developed infectious endophthalmitis (fungal in 2 cases, bacterial in 5 cases) Mean interval from surgery to infection was 11 months (range 1 to 60 months) Treatment of the infected eyes required prosthesis removal in 7 eyes (53.8%), and reduced pre-infection visual acuity in 7 eyes (53.8%) The Boston Kpro-1 is associated with an excellent prognosis for prosthesis retention and satisfactory visual improvement in eyes with previous failed keratoplasty (p 73) The Boston keratoprosthesis type 1 is an effective device for rehabilitation in advanced ocular surface disease, resulting in a significant improvement in visual acuity (p 89) Postoperative infections are a serious issue that compromises device retention and visual outcomes after keratoprosthesis implantation (p 486) Boston Keratoprosthesis for the Treatment of Corneal Blindness 15
First Author, Publication Year Cortina, 21 2015 Table A4: Main Study Findings and Authors Conclusions Using the NEI VFQ-25: Main Study Findings Compared to baseline (pre implantation) values, significant improvement in general vision, near and distance activities, social functioning, mental health, role difficulties, dependency, color vision, and peripheral vision (P < 0.05) (mean 16 months follow-up; range 2-36 months). Authors Conclusions The quality of life of patients who underwent KPro significantly improved postoperatively compared with their preoperative status (p 160) de Oliveira, 22 2014 Muñoz- Gutierrez, 23 2013 VFQ overall score: baseline 44.6; KPro 72.2 (P < 0.0001) Visual acuity (BCVA improvement; mean 32 months follow-up) Post-operative BCVA improved in 24 (80%) eyes Graft retention (mean 32 months follow-up) KPro was retained in in 93.3% Complications (mean 32 months follow-up) 3 eyes developed glaucoma 2 eyes had retinal detachment 1 eye developed infectious keratitis Visual acuity (BCVA improvement; mean 22.17 months followup) Mean BVCA (converted to log): 2.05 (range 1.10 to 2.52) before surgery; 1.16 (range 0.08 2.70) after surgery BVCA was maintained or improved in 34 (82.92%) of patients Complications (mean 22.17 months follow-up) Formation of retroprosthetic memebrane in 22 (53.65%) eyes 2 (4.87%) eyes had infectious keratitis 5 (12.19%) had infectious endophthalmitis Performing Boston type 1 keratoprosthesis in a developing country is a viable option after multiple keratoplasty failures and conditions with a poor prognosis for keratoplasty (p 351) We consider KPro as an effective alternative in patients with multiple ocular pathology and imminent risk of rejection of a new KP (p 56) Research question 2 (cost-effectiveness of the Boston Keratoprosthesis (KPro) for the treatment of corneal blindness) There was no evidence found on the cost-effectiveness of the Boston Keratoprosthesis (KPro) for the treatment of corneal blindness BCVA: best corrected visual acuity; CI: confidence interval; KPro: Boston type 1 keratoplasty; NEI VFQ-25: National Eye Institute Visual Function Questionnaire; PK: penetrating keratoplasty. Boston Keratoprosthesis for the Treatment of Corneal Blindness 16